Zambia, one of the world's poorest countries, has one of Africa's most severe HIV and TB epidemics. HIV prevalence in Lusaka inpatients is 65%, and 29% among pregnant women. TB accounts for 25% of maternal mortality, and is co-diagnosed with HIV in 92% of parturients. AIDS therapies are not available and resources to provide directly observed therapy (DOT) for HIV and TB are lacking. A collaborative Zambian/ U.S. endeavor is developing a consensus research agenda and plans large, simple clinical trials of antiretroviral and prophylactic therapies in line with Zambian realities. We propose to organize the following elements needed before clinical trials can begin: 1) training of Zambian clinical, administrative, data and laboratory personnel to augment capacity and ensure sustainability; 2) development of a model comprehensive home care program to provide DOT nested within both traditional and western care modalities; 3) training and model care programs for the psychosocial aspects of HIV care based on the mobilization of community resources and support; 4) broadening the consensus in the professional, governmental, informal provider, donor, and community stakeholders concerning the role of ART. Since 1995, a comprehensive clinical and administrative infrastructure has been created in Lusaka in collaboration with the University of Alabama at Birmingham to train In-country investigators to implement studies of perinatal and heterosexual HIV transmission prevention. After extensive planning at UAB and in Lusaka, we have assembled an impressive team of investigators committed to build a program of comprehensive HIV care, to augment our present studies in seropositive women and to extend care to their families.